TY  - JOUR
N1  - Copyright of this article belongs to American Society of Hematology.
ID  - open1058
UR  - http://bloodjournal.hematologylibrary.org/content/109/2/653.full.pdf+html
IS  - 2
A1  - Sen, Pradip
A1  - Wallet, Mark A
A1  - Yi, Zuoan
A1  - Huang, Yingsu
A1  - Henderson, Michael
A1  - Mathews, Clayton E
A1  - Earp, H Shelton
A1  - Matsushima, Glenn
A1  - Baldwin, Albert S
A1  - Tisch, Roland M
Y1  - 2007/01/15/
N2  - Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic cells (ACs) and subsequent inhibition of maturation and effector functions. The receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs have yet to be defined. We demonstrate that pretreatment with apoptotic but not necrotic cells inhibits activation of IkappaB kinase (IKK) and downstream NF-kappaB. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required for mediating this effect. Monocyte-derived DCs lacking MerTK expression (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant to AC-induced inhibition and continue to activate NF-kappaB and secrete proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and NF-kappaB pathways in AC-induced inhibition of monocyte-derived DCs.
PB  - American Society of Hematology
JF  - Blood
VL  - 109
SN  - 0006-4971
TI  - Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells.
SP  - 653
AV  - restricted
EP  - 60
ER  -